Discovery and Dissemination PROTEIN-PROTEIN INTERACTIONS Madhavi Ganapathiraju Associate Professor Department of Biomedical Informatics University of Pittsburgh Faculty of Biomedical Informatics Training Program Intelligent Systems Program Integrated Systems Biology Program Joint CMU-Pitt Ph.D. Program in Comp Bio Language Technologies Institute (CMU)

? Protein-Protein Interactions Theme of Research in Madhavi’s Lab Central to all biological processes and structural scaffolds The network is a medium for systems biology research But 90% of protein-protein interactions are unknown today ? ~22,500 protein-coding genes Human Interactome 200,000 to 600,000 PPIs protein-pairs ~250Million possible pairs Our primary research is in predicting protein-protein interactions. I say high confidence, because we want to predict with very high accuracy even if we predict only a few of all true interactions Let’s look at the size of the problem in rough numbers There are some 25000 genes in human If you look at proteins from every pair of these genes, There are more than 300 million pairs Of these only 200 to 600 thousand pairs are interacting proteins And of these, nearly 90% of the interactions are unknown Theme of Research in Madhavi’s Lab Discovery of protein-protein interactions from large data sources using Machine Learning methods Results: 1000’s of Novel PPIs discovered Accurately (c) Madhavi Ganapathiraju

We discovered 1000’s of Novel PPIs Accurately 14 studied by experiments (by collaborators); all 14 validated to be correct

Interactome Analysis of Disease-Associated Genes Shortest Paths between CHD Genes: Mean distance: 4.7; St-dev: 3.3 Between Random Genes: Mean: 14.9;   S-dev:   4.9 CHD Gene Novel Predicted Interaction Previously Known Interaction Immunity, 40(6), 2014. Zhu et al. Nature, 521(7553), 2015. Li et al. npj Schizophrenia 2(16012), 2016 and 3(11) 2017 http://tinyurl.com/MadhaviCMUscholar Other Ongoing Studies Dystonia interactome, & Development of tools and algorithms for analysis and dissemination of these novel PPIs Reveals novel relations to Cilia and to relevant pathways Interactome of Congenital Heart Associated Genes and its overlap with cilia genes Funding: BRAINS Award (1R01MH094564) its supplement